Oncogene:具有短聚谷氨酸尾巴的雄激素受体能够增强Wnt/β-连环蛋白介导的前列腺致瘤过程

2020-03-04 AlexYang MedSci原创

人类雄激素受体(AR)聚谷氨酸(polyQ)尾巴的多样性表明了群体的异质性存在。非裔美国男性要比白种美国男性具有显著更高频率的短polyQ尾巴。polyQ尾巴的长度与前列腺癌风险、起始年龄和诊断时侵入情况呈负相关关系。Wnt信号的异常激活经常在晚期前列腺癌中发生,并且在非裔美国男性中富集雄激素和Wnt信号激活。最近,有研究人员在新建立的小鼠前列腺致瘤模型中评估了AR的异常表达情况,这些小鼠存在不同

人类雄激素受体(AR)聚谷氨酸(polyQ)尾巴的多样性表明了群体的异质性存在。非裔美国男性要比白种美国男性具有显著更高频率的短polyQ尾巴。polyQ尾巴的长度与前列腺癌风险、起始年龄和诊断时侵入情况呈负相关关系。Wnt信号的异常激活经常在晚期前列腺癌中发生,并且在非裔美国男性中富集雄激素和Wnt信号激活。

最近,有研究人员在新建立的小鼠前列腺致瘤模型中评估了AR的异常表达情况,这些小鼠存在不同的polyQ尾巴和稳定的β-连环蛋白。研究发现,在具有短polyQ尾巴和稳定的β-连环蛋白复合小鼠中发生早发的致瘤转化、加速的肿瘤细胞生长以及恶性的肿瘤表型。RNA测序分析表明了具有短polyQ尾巴的AR肿瘤与具有更长的polyQ尾巴的AR肿瘤相比,Myc调控的下游基因具有更多的富集。在上述具有短polyQ尾巴AR和β-连环蛋白小鼠样本中,上游调控分析进一步鉴定了Myc是顶端的候选转录调控因子。染色质免疫沉淀分析阐释了在表达稳定的β-连环蛋白和端polyQ 尾巴AR的肿瘤组织样本中,c-Myc基因调控位点β-连环蛋白和AR招募增加。

最后,研究人员指出,他们的数据阐释了Wnt/β-连环蛋白异常激活结合短polyQ尾巴AR表达在前列腺癌致瘤过程中的促进作用,表明了恶性前列腺肿瘤发育过程中的一个潜在机制,上述情况也在非裔美国患者中经常出现。

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    2021-01-19 liubm568
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    2020-07-02 cy0324
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    2020-03-06 zhwj

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